Project Summary/Abstract The Translational and Clinical Sciences Program enables USC Norris discoveries to be translated to the clinic by conducting innovative trials relevant to our patient population. Members have diverse expertise from basic to clinical investigation and are highly engaged. Leadership is enriched by an inter-programmatic Steering Committee, which leverages expertise in genomics, biomarkers, bio-imaging and drug development, and regular meetings with disease and thematic teams to ensure that translational and clinical research occurs in an interdisciplinary and coordinated manner. New targets are selected from basic science Research Programs, with translation supported and accelerated by collaborative teams focused on developing novel therapeutics, diagnostics and biomarkers and on executing clinical trials. Members actively participate in intra- and inter- programmatic research using the expertise of USC Norris Shared Resources and clinical resources. Priority themes are novel targets, enhanced efficacy of antibodies using drug conjugates, immunotherapeutics, and cell therapies, and epigenetic targets. We have identified and validated tumor-associated targets, developed agents that have been taken to first in human studies, developed companion imaging agents, and initiated multiple high priority investigator initiated trials. Several novel targets have been chosen and moved through different stages of translation that are already or soon to be in the clinic. Accompanying biomarkers and imaging probes have also been developed for several targets and integrated into trials. Multiple high-impact trials have been conducted, including first in human novel agents discovered and developed at USC Norris and positive Phase II trials that have moved to Phase III. USC Norris PIs have served as lead investigators for several multicenter Phase III NCTN trials. The Program's 61 members come from six schools and 21 departments. They have $16M in total funding (direct costs) of which 31% is from NCI, 25% is from other NIH sources, and 13% from other peer-reviewed funding sources. The Program has been highly productive with 1,030 publications during the project period, of which 27% were intra-programmatic, 31% were inter- programmatic and 42% were inter-institutional.